Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease

Hong Jun Cho, Truc T. Huynh, Buck E. Rogers, Liviu M. Mirica

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Herein, we report a 64Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood-brain barrier penetration, while the use of optimized-length spacers between the Cuchelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding 64Cu PET imaging agent.

Original languageEnglish
Pages (from-to)30928-30933
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number49
DOIs
StatePublished - Dec 8 2020

Keywords

  • Alzheimer's disease
  • Amyloid beta (Aβ) peptide
  • Blood-brain barrier
  • Multivalent effect
  • Positron emission tomography imaging

Fingerprint

Dive into the research topics of 'Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease'. Together they form a unique fingerprint.

Cite this